• 1
    Blumberg BS, Alter HJ. Visnich? A “new” antigen in leukemia sera. JAMA 1965; 191: 5416.
  • 2
    Dienes HP, Gerlich WH, Worsdorfer M, et al. Hepatic expression patterns of the large and middle hepatitis B surface proteins in viremic and non viremic chronic hepatitis B. Gastroenterology 1990; 98: 101723.
  • 3
    Lau JYN, Bain VG, Davies SE, et al. Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication. Hepatology 1991; 14: 41621.
  • 4
    Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med 2004; 350: 11829.
  • 5
    Werle-Lapostolle B, Bowden S, Locarnini S, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004; 126: 17508.
  • 6
    Chan HL, Wong VW, Tse AM, et al. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol 2007; 5: 14628.
  • 7
    Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010; 52: 51422.
  • 8
    Janssen HLA, Kerhof-Los CJ, Heijtink RA, Schalm SW. Measurement of HBsAg to monitor hepatitis B viral replication in patients on α-interferon therapy. Antivir Res 1994; 23: 2517.
  • 9
    Chan HL, Thompson A, Martinot-Peignoux M, et al. Hepatitis B surface antigen quantification: why and how to use it in 2011-A core group report. J Hepatol 2011; 55: 112131.
  • 10
    Martinot-Peignoux M, Asselah T, Marcellin P. HBsAg quantification to predict natural history and treatment outcome in chronic hepatitis B patients. Clin Liver Dis 2013; 17: 399412.
  • 11
    Wursthorn K, Jaroszewicz J, Zacher BJ, et al. Correlation between the Elecsys HBsAg II assay and the architect assay for quantification of hepatitis B surface antigen (HBsAg) in serum. J Clin Virol 2011; 50: 2926.
  • 12
    Sonneveld MJ, Rijckborst V, Boucher CAB, et al. A comparison of two assays for quantification of hepatitis B surface antigen in patients with chronic hepatitis B.. J Clin Virol 2011; 51: 1758.
  • 13
    Martinot-Peignoux M, Lapalus M, Asselah T, Marcellin P. The role of HBsAg quantification for monitoring the natural history and treatment out come. Liver Int 2013; 33(Suppl. 1): 12532.
  • 14
    Janssen HLA, Sonneveld M, Brunetto MR. Quantification of serum hepatitis B surface antigen: is it useful for the management of chronic hepatitisB? Gut 2012; 61: 6415.
  • 15
    Chudy M, Scheiblauer H, Hanschman KM, et al. Performance of hepatitis B surface antigen tests with the first WHO international hepatitis B virus genotype reference panel. J Clin Virol 2013; 58: 4753.
  • 16
    Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010; 52: 50813.
  • 17
    Martinot-Peignoux M, Lapalus M, Lada O, et al. Natural history of hepatitis B (HBV) infection: role of HBV genotype (A to E) assessed in a large cohort. Hepatology 2011; 54(Suppl.): 609A.
  • 18
    Araujo NM, Vianna COA, Moraes MTB, et al. Expression of hepatitis B virus surface antigen (HBsAg) from genotypes A, D and F and influence of amino acid variations related or not to HBsAg detection. Braz J Infect Dis 2009; 13: 26671.
  • 19
    Martinot-Peignoux M, Boyer N, Colombat M, et al. Serum hepatitis B virus HBV DNA levels and liver histology in inactive HBsAg carriers. J Hepatol 2002; 36: 5436.
  • 20
    Brunetto MR, Oiveri F, Coco B, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon and untreated patients: a long term cohort study. J Hepatol 2002; 36: 26370.
  • 21
    Lok A, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000-summary of a workshop. Gastroenterology 2001; 120: 182853.
  • 22
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2012; 50: 22742.
  • 23
    Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum HBsAg changes in chronic hepatitis B. Hepatology 2010; 52: 123241.
  • 24
    Chan HL, Wong GL, Tse CH, et al. Definition of inactive hepatitis B carrer by serum HBsAg and HBV DNA levels – a long-term follow-up study on HBsAg seroclearance. J Hepatol 2011; 54: S144.
  • 25
    Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010; 139: 48390.
  • 26
    Martinot-Peignoux M, Lapalus M, Laouénan C, et al. Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA. J Clin Virol 2013; 58: 4017.
  • 27
    Lui J, Yang HI, Lee MH, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2012; 139: 47482.
  • 28
    Lui J, Lee MH, Batrla-Utermann R, et al. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol 2013; 58: 84560.
  • 29
    Chen YC, Jeng WJ, Chu CM, Liaw YF. Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2012; 10: 297302.
  • 30
    Seto WK, Wnog DKH, Fung J, et al. High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B. PLoS ONE 2012; 7: e43087.
  • 31
    Martinot-Peignoux M, Carvalho RJ, Lapalus M, et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naive, e-antigen-positive patients. J Hepatol 2013; 58: 108995.
  • 32
    Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 6573.
  • 33
    Lee MH, Yang HI, Liu J, et al. Prediction model of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk score integrating host and virus profiles. Hepatology 2013; 58: 54654.
  • 34
    Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HCV load. Gastroenterology 2012; 142: 11409.
  • 35
    Tseng TC, Liu CJ, Yang HC, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus load. Hepatology 2013; 57: 44150.
  • 36
    Lau GKK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamuvidine, and the combination for HbeAg-positive chronic hepatitis B. N Engl J Med 2005; 352: 268295.
  • 37
    Marcellin P, Lau GKK, Bonino F, et al. Peginterferon alfa-2a, lamuvidine, and the two in combination for HBeAg-negative chronic hepatitis B. N Engl J Med 2004; 351: 120617.
  • 38
    Chan HL, Wong VW, Chim AM, et al. Serum HBsAg quantification to predict response to peginterferon therapy of e antigen positive chronic hepatitis B. Aliment Pharmacol Ther 2010; 32: 132331.
  • 39
    Tangkijvanich P, Komolmit P, Mahachai V, et al. Low pretreatment serum HBsAg level and viral mutations as predictors of response to Peginterferon alfa-2b therapy in chronic hepatitis B. J Clin Virol 2009; 46: 11723.
  • 40
    Lau G, Marcellin P, Brunetto M. On treatment monitoring of HBsAg levels to predict response to peginterferon alfa-2a in patients with HBeAg-positive chronic hepatitis B. J Hepatol 2009; 50: S333.
  • 41
    Gane E, Jia J, Han K, et al. NEPTUNE study; on treatment HBs Ag level analysis confirms prediction of response observed in phase 3 study of peginterferon alfa-2a in HBeAg positive patients. J Hepatol 2011; 54: Abstract 69.
  • 42
    Sonneveld MJ, Rijckborst V, Boucher CA, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology 2010; 52: 12517.
  • 43
    Piratvisuth T, Marcellin P. Further analysis is required to identify an early stopping rule for peginterferon therapy that is valid for all HBeAg-positive patients. Hepatology 2011; 53: 10545.
  • 44
    Flink HJ, van Zonneveld M, Hansen B, et al. treatment with Peg-Interferon a-2a for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype? Am J Gastroenterol 2006; 101: 297303.
    Direct Link:
  • 45
    Soneveld MJ, Rijckborst V, Cakaloglu Y, et al. Durable hepatitis surface antigen decline in hepatitis B e antigen positive chronic hepatitis B patients treated with pegylated interferon-a2b: relation to response and HBV genotype. Antivir Ther 2012; 17: 917.
  • 46
    Moucari R, Martinot-Peignoux M, Mackiewicz V, et al. Influence of genotype on hepatitis B surafce antigen in hepatitis B e antigen-negative patients trated with pegylated interferon-alpha-2a. Antivir Ther 2009; 14: 11838.
  • 47
    Brunetto MR, Marcellin P, Cherubin B, et al. Response to peginterferon alfa-2a(40KD) in HBeAg-negative CHB: ontreatment kinetics of HBsAg serum levels vary by HBV genotype. J Hepatol 2013; 59: 11539.
  • 48
    Sonneveld MJ, Hansen BE, Piratvisuth T, et al. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis surface antigen levels. Hepatology 2013; 3: 87280.
  • 49
    Hadziyannis SJ. Treatment paradigms on hepatitis Be antigen negative chronic hepatitis B patients. Expert Opin Investig Drugs 2007; 16: 77786.
  • 50
    Rijckborst V, Hansen BE, Cakaloglu Y, et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology 2010; 52: 45461.
  • 51
    Marcellin P, Bonino F, Yurdayin C, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitid Be antigen-negative patients. Hepatol Int 2013; 7: 8897.
  • 52
    Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 2009; 49: 11517.
  • 53
    Brunetto MR, Moriconi F, Bononi F, et al. Hepatitis B virus surface antigen levels: a guide to sutained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 2009; 49: 114150.
  • 54
    Moucari R. Peginterferon for chronic hepatitis B: predicting success with on-treatment benchmarks. J Gastroenterol Hepatol 2010; 25: 14745.
  • 55
    Moucari R, Korevaar A, Lada O, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol 2009; 50: 108492.
  • 56
    Lampertico P, Liaw YF. New perspectives in the therapy of chronic hepatitis B. Gut 2012; 61(Suppl. 1): i1824.
  • 57
    Rijckborst V, Hansen BE, Ferenci P, et al. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alpha-2a. J Hepatol 2012; 6: 100611.
  • 58
    Lampertico P, Vigano P, Di Costanzo G, et al. Extended (2 years) treatment with peginterferon alfa-2a improves sustained response rates in genotype D patients with HBeAg negative chronic hepatitis B. J Hepatol 2010; 52: S45.
  • 59
    Iannazzo S, Coco B, Brunetto MR, et al. Individualized treatment of HbeAg-negative chronic hepatitis B using pegylated interferon -a2a as first line and weel-12 HBVDNA/HBsAg stopping rule; a cost-effectiveness analysis. Antivir Thar 2013; 18: 62333.
  • 60
    Manesis EK, Hadziyannis ES, Angelopoulou OS, Hadziyannis SJ. Prediction of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther 2007; 12: 7382.
  • 61
    Reijnders JG, Rijckborst V, Sonneveld MJ, et al. Kinetics of hepatits B surface antigen differ between treatment with peginterferon and entecavir. J Hepatol 2011; 54: 44954.
  • 62
    Boglione L, D'Avolio A, Cariti G, et al. Kinetics and prediction of HBsAg loss during therapy with analogues i patients affected by chronic hepatitis B HBeAg negative and genotype D. Liver Int 2013; doi:10.1111/liv.12091.
  • 63
    Lee JM, Ahn SH, Kim HS, et al. Quantitative hepatitis B surface antigen and hepatitis B e atigen titers in prediction of treatment response to entecavir. Hepatology 2011; 53: 148693.
  • 64
    Chen J, Wang Z, Zhou B, et al. Factors associated with hepatitis B surface antigen levels and its on-treatment changes in patients under lamivudine therapy. Antivir Ther 2012; 17: 719.
  • 65
    Wursthorn K, Jung M, Riva A, et al. Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients. Hepatology 2010; 52: 161120.
  • 66
    Gramenzi A, Loggi E, Micco L, et al. Serum hepatitis B surface antigen monitiring in long-term lamuvudine-treated hepatitis B virus patients. J Viral Hepat 2011; 10: 46874.
  • 67
    Zoulim F, Carosi G, Greenbloom S, et al. Quantification of HBsAg in nucleos(t)ides-naive patients treated for chronic hepatitis B with entecavir or entecavir plus tenofovir in the BE-LOW study. J Viral Hepat 2012; 19(Suppl. S3): O224.
  • 68
    Zoutendijk R, Hansen BE, Van Vuuren AJ, et al. Serum HBsAg decline during long-term potent nucleos(t)ideanalogue therapy for chronic hepatitis B and prediction of HBsAg loss. JID 2011; 204: 4158.
  • 69
    Marcellin M, Heathcote EJ, Buti M, et al. Tenofovir disiproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008; 359: 244255.
  • 70
    Heathcote EJ, Marcellin M, Buti M, et al. Three years efficacy and safety of Tenofovir Disiproxil Fumarate treatment for chronic hepatitis B. Gastroenterology 2011; 140: 13243.
  • 71
    Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B:5-year open-label follow-up study. Lancet 2013; 381: 46875.
  • 72
    Woo G, Tomlinson G, Nishikawa Y, et al. Tenofovir and entecavir are the most effective antiviral agent for chronic hepatitis B: a systematic review and bayesian meta-analysis. Gastroenterology 2010; 139: 121829.
  • 73
    Chevaliez S, Hezode C, Baharami S, et al. LOng-term hepattitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite duration of treatment unlikely. J Hepatol 2013; 58: 67683.
  • 74
    Liang Y, Jiang J, Su M, et al. Predictors of relapse in chronic hepatitis B after discontinuation of antiviral therapy. Aliment Pharmacol Ther 2011; 34: 34452.
  • 75
    Petersen J, Hansen BE, Buggisch P, et al. Discontinuation long-term nucleos(t)ide analogue therapy before HBsAg loss in HBeAg negative CHB patients: follow-up of long-term responders. Hepatology 2013; 58(Suppl. 1): 132A.
  • 76
    Cai W, Xie Q, An B, et al. On-treatment serum HBsAg level is predictive of sustained off-treatment virologic response to telbivudine in HBeAg-positive chronic hepatitis B patients. J Clin Virol 2010; 48: 226.
  • 77
    Seto WK, Wong DKH, Fung J, et al. Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleotside analogue therapy. Hepatology 2013; doi:10.1002/hep.26376.
  • 78
    Seto WK, Lui K, Wong DKH, et al. Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatment experienced chronic hepatitis B patients after three years of tenofovir treatment. J Hepatol 2013; 59: 70916.
  • 79
    Gish RG, Chang TT, Lai CL, et al. Quantitative hepatitis B surface antigen analysis in hepatitis B e antigen-positive, nucleoside-naïve patients treated with entecavir. Antivir Ther 2013; doi:10.3851/IMP2559.
  • 80
    Sonneveld ML, Qing X, Zhang NP, et al. Adding peginterferon alfa-2a to entecavir increases HBsAg decline and HBsAg clearance-first results from a global randomized trial. Hepatology 2012; 4(Suppl.): 199A.
  • 81
    Marcellin P, Martinot-Peignoux M, Lapalus M, et al. Predictive value of qHBsAg for SVR and HBsAg loss in chronic hepatitis B patients receiving pegylated inteferon with or without teneofovir. Hepatology 2013; 58(Suppl. 1): 132A.
  • 82
    Takkenberg RB, Jansen L, de Net A, et al. Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with peginterfeon and adefovir. Antivir Ther 2013; doi:10.3851/IMP2580.
  • 83
    Ouzan D, Penaranda G, Joly H, et al. Add-on-peg-interferon leads to loss of HBsAg in patients with HBe-negative chronic hepatitis HBV DNA fully supressed by lon-term nucleotide analogs. J Clin Virol 2013; doi: